Our studies have shown that the rate limiting step governing carbohydrate catabolism in the isolated gastric mucosa of the frog is the conversion of pyruvate to acetyl CoA. The inability of intermediates of glycolysis to stimulate respiration and acid secretion was overcome by adding lipoate, one of the coenzymes of pyruvate dehydrogenase. Unexpectedly the resultant increase in carbohydrate catabolism was accompanied by a decrease in fatty acid oxidation. Our future efforts are designed to further delineate the ways in which lipoate enhances carbohydrate catabolism and to see whether lipoate inhibits the respiratory and secretory responses to fatty acids either by a direct effect of lipoate on fatty acid oxidation or due to its enhancement of carbohydrate catabolism. The experiments will evaluate the competition between pyruvate and palmitate for oxidation in the untreated mucosa and characterize lipoate's enhancement of pyruvate and palmitate oxidation. The studies will be extended to examine the effect of lipoate on pyruvate and fatty acid oxidation in gastric mitochondria. Finally, we will see if the findings demonstrated in the gastric mucosa can be elicited in mammalian tissues such as skeletal muscle, renal cortex and the liver of the rat.